Abstract
We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-A*01/Kb Tg mice with rVV-SIVGag-Pol, the mice generated CD8+ T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/Kb Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 16-28 |
| Number of pages | 13 |
| Journal | Virology |
| Volume | 387 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 25 2009 |
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Keywords
- Cellular immunity
- Mamu A*01
- Peptide vaccine
- Poxvirus challenge
- SIV
- Transgenic mouse model
ASJC Scopus subject areas
- Virology
Cite this
Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development. / Li, Jinliang; Srivastava, Tumul; Rawal, Ravindra; Manuel, Edwin; Isbell, Donna; Tsark, Walter; La Rosa, Corinna; Wang, Zhongde; Li, Zhongqi; Barry, Peter A; Hagen, Katharine D.; Longmate, Jeffrey; Diamond, Don J.
In: Virology, Vol. 387, No. 1, 25.04.2009, p. 16-28.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development
AU - Li, Jinliang
AU - Srivastava, Tumul
AU - Rawal, Ravindra
AU - Manuel, Edwin
AU - Isbell, Donna
AU - Tsark, Walter
AU - La Rosa, Corinna
AU - Wang, Zhongde
AU - Li, Zhongqi
AU - Barry, Peter A
AU - Hagen, Katharine D.
AU - Longmate, Jeffrey
AU - Diamond, Don J.
PY - 2009/4/25
Y1 - 2009/4/25
N2 - We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-A*01/Kb Tg mice with rVV-SIVGag-Pol, the mice generated CD8+ T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/Kb Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.
AB - We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-A*01/Kb Tg mice with rVV-SIVGag-Pol, the mice generated CD8+ T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/Kb Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.
KW - Cellular immunity
KW - Mamu A01
KW - Peptide vaccine
KW - Poxvirus challenge
KW - SIV
KW - Transgenic mouse model
UR - http://www.scopus.com/inward/record.url?scp=63649096920&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63649096920&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2009.01.041
DO - 10.1016/j.virol.2009.01.041
M3 - Article
C2 - 19249807
AN - SCOPUS:63649096920
VL - 387
SP - 16
EP - 28
JO - Virology
JF - Virology
SN - 0042-6822
IS - 1
ER -